ABSTRACT
The expression of a variety of proteins is elevated with aging through unknown mechanisms. The free radical theory of aging promulgates that reactive oxygen species (ROS) promote the aging process. However, the mechanisms as to how ROS contribute to the aging process are not clear. We present data here that demonstrate that aging induced ROS promote aging-associated interleukin-6 (IL-6) gene transcription in mice that are transgenic for the murine IL-6 promoter driving a luciferase reporter cDNA. N-acetylcysteine (NAC), an antioxidant, completely reverses the increased endogenous IL-6 promoter activity in the old mice determined by real-time bioluminescence imaging (BLI). We conclude that ability of ROS to act as secondary messengers and induce gene expression may contribute to the aging process.
Subject(s)
Aging/genetics , Reactive Oxygen Species/pharmacology , Transcription, Genetic/physiology , Acetylcysteine/pharmacology , Aging/physiology , Animals , Free Radical Scavengers/pharmacology , Gene Expression , Interleukin-6/biosynthesis , Interleukin-6/blood , Interleukin-6/genetics , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mitosis , Muscle, Skeletal/metabolism , NF-kappa B/metabolism , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Transcription, Genetic/drug effects , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
The zebrafish (Danio rerio) has proven an excellent model for study of vertebrate development and genetics. Mutagenesis studies have produced many blood mutants with defects ranging from hematopoiesis to coagulation. The overwhelming majority of zebrafish studies have focused on development and mutational effects in embryos, whereas effects in mature zebrafish have gone largely unexplored. We believe that zebrafish will prove a valuable model for study of aging and age-related diseases, and we have sought to characterize some of the basic features of mature zebrafish. Accordingly, blood was collected from adult zebrafish and was analyzed to determine reference hematologic and biochemical parameters. White blood cell differential counts indicated predominantly lymphocytes, with mean proportion of 82.95%. Total red blood cell counts averaged 3.02 x 10(6) cells/microl. Except for increases in alanine transaminase (ALT), amylase, and phosphorus values, serum biochemical analytes were within the range of reported values for mammals and other species of fish. Accurate analysis of the many zebrafish mutants generated requires determination of normal characteristics of zebrafish. We believe results such as these will help define normal adult zebrafish, which have a tremendous potential for use in the study of human disease and aging.
